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C Cordon-Cardo

Publications and source records attributed to C Cordon-Cardo.

At least 217 records · Page 12Linked to original sources
PubMed1989

Tissue distribution of GD3 ganglioside detected by mouse monoclonal antibody R24.

Mouse monoclonal antibody (MoAb) R24 detects the disialoganglioside GD3, a neuroectodermal antigen expressed by normal melanocytes and melanomas. This antibody has been used to define the immunohistochemical distribution of GD3 antigen in normal and malignant human tissues. The present study shows that staining with MoAb R24 in normal organs and tissues where low concentrations of the antigen can be detected. The highest expression of GD3 was detected on the surface of melanoma cells. Therefore, MoAb R24 can be a useful reagent for studying cells of melanocytic lineage, and for imaging and therapeutic studies of melanomas.

Animals↗
PubMed1989

Analysis of ras oncogenes in malignant melanoma and precursor lesions: correlation of point mutations with differentiation phenotype.

This study examined noncultured and cultured melanomas and related precursor specimens for (i) mutated ras genes using polymerase chain reaction (PCR) methodology, (ii) correlation of mutated ras genes with differentiation related phenotypic characteristics, (iii) expression of ras-encoded p21 proteins in tissues by immunoperoxidase analysis, (iv) quantitative expression of mutated and wild-type ras encoded p21 proteins by flow cytometry, and (v) correlation between p21 expression, the occurrence of ras mutations, and cell cycle kinetics. The results of these studies are (1) 24% of cultured malignant melanomas have activated ras genes, with N-ras being activated ten times as frequently as Harvey (Ha)-ras. Each example of an activated ras gene showed a mutation at the 61st codon of the protein, with the exception of one melanoma which showed a mutation at codon 13 of the N-ras gene; (2) all the melanomas displaying an activated ras gene had a similar cell surface phenotype and appear to come from a similar phase of differentiation; (3) 5-6% of noncultured primary and metastatic melanomas have mutated ras genes; (4) no ras gene mutations were found in any precursor lesion, specifically normal nevi and dysplastic nevi; (5) immunoperoxidase analysis of paraffin-embedded specimens indicated no quantitative or qualitative alterations in p21 expression that correlate with tumor progression; (6) there were no observable differences in p21 expression between melanoma cells growing exponentially or in plateau phase, or between melanoma cells with or without ras mutations; nor were any cell kinetic differences found between cells with and without mutated ras genes. These studies suggest that the role of ras mutations may be limited to an indirect involvement in the transformation of a subset of melanomas.

Animals↗
PubMed1989

Restricted expression of an early myeloid and monocytic cell surface antigen defined by monoclonal antibody M195.

A mouse monoclonal IgG2a antibody, M195, with reactivity restricted to early myeloid cells, acute non-lymphoid leukemia cells (ANLL), and monocytic cells is described. The antibody was derived from a mouse immunized with live human leukemic myeloblasts. Specificity of binding of mAb M195 was determined by protein-A red blood cell rosetting assays, immunoabsorption, radioimmunoassays with iodine-125 labeled M195 IgG and F(Ab)'2, and complement cytotoxicity with live human cells and cell lines representing a broad range of lineages and tissues. Antigen expression was restricted to myeloid and monocytic leukemia cell lines and a fraction of mature adherent monocytes. Mature myeloid cells, T and B cells, erythrocytes, and platelets were negative. The antigen was not expressed on adult human tissues in immunoperoxidase and immunofluorescence assays. Blocking antigen was not found in the serum of patients with ANLL. Ten thousand sites per cell were expressed on myeloid or monocytic leukemia cell lines and 5000 sites per cell on mature monocytes. M195 IgG bound to its antigen target with an avidity of 3 x 10(9) liters/mol and induced rapid modulation of the antigen. M195 IgG was able to effectively kill cells with rabbit or guinea pig complement, but not human complement. The antibody did not mediate antibody dependent cellular cytotoxicity. The molecular nature of the target antigen remains unknown but it appears to be carried on the CD33 protein p67. Because of its restricted distribution on myelomonocytic cells, mAb M195 may be useful in studying myeloid differentiation, in the clinical diagnosis of ANLL, in purging of bone marrow of ANLL, and/or in monoclonal antibody therapy in vivo.

Animals↗
PubMed1988

Immunohistochemical characterization of two monoclonal antibodies, P25.48 and P25.91, which define a new prostate-specific antigen.

We have generated two new mouse monoclonal antibodies against prostate cancer. P25.48 (IgG3) and P25.91 (IgG2a) were derived from a fusion using fresh prostate cancer cells as the immunogen. Initial screening was performed by indirect immunofluorescence on frozen tissue sections of prostate cancer specimens. The specificity analysis was performed by indirect immunoperoxidase on frozen sections of normal tissues and benign and malignant prostate tissues. P25.48 and P25.91 did not react with any benign prostatic tissues (0 of 17), but reacted with a subset of the malignant prostatic tissues. Five specimens of well-differentiated carcinoma were tested and did not react with P25.48 or with P25.91. Of 16 higher grade specimens, nine reacted with both P25.48 and P25.91, one reacted with P25.48 only, and one reacted with P25.91 only. In most positive cases, the reactivity was heterogenous. P25.48 and P25.91 showed a very restricted pattern of reactivity in nonprostatic tissues. Of 50 normal specimens, only one breast specimen showed some reactivity. None of the nine fetal tissues or of the 15 malignant tissues tested reacted with these monoclonal antibodies. The pattern of reactivity of P25.48 and P25.91 suggests that they recognize the same antigen. This antigen is selectively expressed by malignant prostatic epithelium. In addition, it appears to be distinct from all other previously described prostate cancer-associated antigens.

Antibodies, Monoclonal↗
PubMed1988

Blood group-related antigens in human germ cell tumors.

With the use of immunohistochemical techniques, seven mouse monoclonal antibodies and the lectin from Ulex europaeus, detecting blood group antigens of the ABH and Lewis systems, have been used to define the distribution of these antigenic structures in germ cell tumors. The reagents used recognize the following blood group antigens: A, B, H, Lewisa, Lewisb, X (Lewisx), Y (Lewisy), and type I precursor antigen. Tumors from 29 patients were studied. Tumors studied consisted of pure embryonal carcinoma for eight patients, pure yolk sac tumor for two patients, embryonal carcinoma plus yolk sac tumor in one patient, and yolk sac tumor plus seminoma in one patient. Also studied were nine classic seminomas and a group of six patients with tumors classified as seminomas that exhibited atypical histological features. One patient had an anaplastic carcinoma arising from the mediastinum which could not be conclusively identified as a germ cell tumor morphologically and was analyzed separately. All embryonal carcinomas and yolk sac tumors exhibited strong positivity for type I precursor structure as detected by the K-21 monoclonal antibody. In marked contrast, there was non staining in classic seminomas but heterogeneous staining in five of six atypical seminomas. The majority of embryonal carcinomas and all yolk sac tumors studied demonstrated strong positivity for blood group antigen H. For seminoma, however, only one of the atypical cases and two of the classic cases (occasional cells) stained for H. Focal expression of the Y antigen was identified in 5 of 17 seminomas and in the majority of embryonal carcinomas and yolk sac tumors. Two yolk sac tumors and two classic seminomas expressed blood group X. The remaining blood group antigens were not expressed by seminomas while they were variably expressed by embryonal carcinoma and yolk sac tumors. These data suggest that K-21 and blood group antigen H may be distinguishing markers of nonseminomatous germ cell tumor versus seminoma. If so, it is possible that the heterogeneous expression of blood group substances in seminomas with atypical histologies is an indication of differentiation towards nonseminomatous germ cell tumor.

ABO Blood-Group System↗
PubMed1988

Blood group-related antigens in human urothelium: enhanced expression of precursor, LeX, and LeY determinants in urothelial carcinoma.

Seven mouse monoclonal antibodies and the lectin from Ulex europaeus, detecting blood group specificities of the ABH and Lewis systems, have been used to define the expression and/or modulation of these antigenic structures in human normal urothelium and tumors of the urinary bladder. The reagents employed recognize the following blood group related antigens: A, B, H, Lewisa (Lea), Lewisb (Leb), Lewisx (Lex), Lewisy (Ley), and type 1 precursor chain. Immunohistochemical studies have demonstrated that these antigenic systems are differentially expressed in the urothelium of secretor and nonsecretor individuals. The normal urothelium of secretors is particularly rich in ABH blood group antigens as well as Leb and Ley specificities. Nonsecretors, however, either lack or show decreased and patchy expression of H, Leb, and Ley antigens. In general, areas affected by carcinoma in situ showed deletion of ABH, as did invasive carcinomas, as demonstrated by other investigators. This was not a universal observation, however, as variable expression of ABH antigens occurred in a few invasive tumors. Lex antigen was not expressed in normal urothelium except for occasional umbrella cells, but was demonstrated in the majority of invasive tumors, regardless of blood type and secretor status of the individuals studied. Ley determinant, which was poorly expressed in the normal urothelium of nonsecretor individuals, was found in all tumors analyzed. An accumulation of non-fucosylated precursor structure was also a feature of invasive carcinoma, particularly in secretor individuals. A panel of anti-blood group antibodies, encompassing A, B, Lex, Ley and type 1 precursor chain specificities for use in patients of known secretor status, may provide useful early markers of malignant change in the urothelium.

Adult↗
PubMed1988

Cell surface antigens of human melanocytes and melanoma. Expression of adenosine deaminase binding protein is extinguished with melanocyte transformation.

It has been proposed that the pathogenesis of melanoma proceeds through multiple stages, ranging from benign proliferation of melanocytic cells to acquisition of the capacity to invade tissues and metastasize. During investigations of cell surface antigens expressed by melanocytes and melanoma, we identified an antigen system that was expressed by cultured normal melanocytes but not by melanoma cell lines. mAbs against this antigen detected a 120-kD cell surface glycoprotein on melanocytes. This molecule had been identified previously as the binding protein for adenosine deaminase (ADAbp). ADAbp was expressed by 51 melanocyte cell lines derived from normal fetal, newborn, and adult skin and adult choroid, but not by 102 melanoma cell lines derived from primary and metastatic lesions. Studies with radiolabeled bovine adenosine deaminase, confirmed that melanocytes expressed binding sites for adenosine deaminase, but no binding sites were detected on cultured melanoma cells. Further studies showed that ADAbp+ melanocytes became ADAbp- upon malignant transformation in vitro. Immunohistochemical studies on a panel of frozen tissues demonstrated reactivity of anti-ADAbp mAbs with epidermal melanocytes and benign junctional nevi, but not with potentially premalignant dysplastic nevi or primary/metastatic melanoma lesions. These studies demonstrate that ADAbp expression is lost with malignant transformation of melanocytes, presumably at an early stage in the transformation process.

Adenosine Deaminase↗
PubMed1988

Class 1 (unique) tumor antigens of human melanoma: identification of unique and common epitopes on a 90-kDa glycoprotein.

Antibodies present in the serum of melanoma patient FD detect an antigenic determinant (FD) restricted to the autologous melanoma cell line SK-MEL-131. This cell-surface determinant is carried on a glycoprotein of 90 kDa, designated gp90. Mice were immunized with a partially purified preparation of gp90 derived from SK-MEL-131 clone 1.5, and three murine hybridomas (KF23, KF26, and KF104) secreting monoclonal antibodies (mAbs) detecting this antigen have been generated. Sequential immunoprecipitation experiments demonstrate that the three mAbs and human FD serum react with the same gp90 species. The mAbs, in contrast to FD serum, react with a broad range of cultured cells in assays for cell-surface antigens and immunoprecipitate a gp90 component from radiolabeled extracts of these cells, including autologous FD B cells. We conclude that gp90 from SK-MEL-131 has two types of determinants: restricted (detected by FD serum) and common (detected by the mouse mAbs). gp90 molecules from cell lines other than SK-MEL-131 carry only the common determinant(s). Immunoperoxidase analysis of frozen tissue sections with mAb KF23 demonstrated a restricted gp90 expression in normal tissues (capillary endothelial cells, duct epithelium in sweat glands, breast, and pancreas). Melanomas and sarcomas showed strong gp90 expression, suggesting up-regulation of gp90 synthesis in certain human cancers.

Animals↗
PubMed1988

Differentiation antigens of melanocytes and melanoma: analysis of melanosome and cell surface markers of human pigmented cells with monoclonal antibodies.

Three mouse monoclonal antibodies (mAbs) recognizing antigens of human melanocytic cells were used to study a large panel of cultured normal and tumor cells and fresh tissues. Two of the monoclonal antibodies (designated TA99 and CF21) detect melanosomal antigens, whereas mAbC350 recognizes a cell surface antigen. Among cultured cells the three mAbs reacted exclusively with normal melanocytes and pigmented melanomas, but not with nonpigmented melanomas or cells of other lineage. Immunohistochemical assays using mAbTA99 and mAbCF21 on fresh-frozen sections from a large panel of normal tissues revealed a characteristic pattern of reactivity restricted to pigmented cells. mAbC350 did not react with any normal tissues. All nevi and primary melanoma specimens and 93% of metastatic melanomas were reactive with at least one of these three monoclonal antibodies. No reactivity was found with 62 nonmelanoma tumors. An inverse correlation was observed between TA99 expression and stage of tumor progression. These markers are useful for studies of melanocyte differentiation and malignant transformation, subsetting of melanocytic lesions, and identification of tumors of melanocytic origin.

Antibodies, Monoclonal↗
PubMed1988

Phase I trial of a mouse monoclonal antibody against GD3 ganglioside in patients with melanoma: induction of inflammatory responses at tumor sites.

Twenty-one patients were entered into a phase I trial to evaluate toxicity, antitumor effects, and biological responses at tumor sites during treatment of R24, an immunoglobulin G3 (IgG3) mouse monoclonal antibody (mAb) against GD3 ganglioside. Toxicity was related to dose of R24. Urticaria and pruritus were the most prominent side effects, with nausea, vomiting, and diarrhea occurring at the highest dose levels. Partial responses were observed in four patients lasting from 6 to 46 weeks, and mixed responses were seen in two patients. Responses occurred as early as 4 weeks and as late as 10 weeks after beginning treatment. Twenty of the 21 patients developed human IgG antibodies against R24. Antimouse Ig antibodies were first detected at a median of 14 days after starting treatment, but three of the four patients who had a partial response developed the antimouse Ig responses later than 20 days. Peak serum levels of R24 were related to dose and ranged from a mean of 0.9 micrograms/mL at the lowest dose level (1 mg/m2/d) to 44 micrograms/mL at the highest dose (50 mg/m2/d). The amount of R24 reaching tumor sites corresponded to the dose administered, and R24 could be detected in tumors as late as 30 days after finishing treatment. Inflammation at tumor sites was observed during treatment. Biopsies of tumors taken before, during, and after treatment revealed that R24 induced deposition of complement components, increased numbers of mast cells with mast cell degranulation, and infiltration of T lymphocytes. These results suggest that treatment with R24 can produce a localized inflammatory response at tumor sites that is capable of producing tumor regression.

Adult↗
PubMed1987

Stimulation of T lymphocyte proliferation by monoclonal antibodies against GD3 ganglioside.

Cell-surface gangliosides are presumed to play a role in cell growth and differentiation. With the use of monoclonal antibodies directed against GD3, a disialoganglioside expressed predominantly by cells of neuroectodermal origin, we have found that GD3 is expressed by a subpopulation of cells of the immune system including: 1) fetal thymocytes in subcortical regions and near vessels, 2) lymph node lymphocytes in interfollicular areas and near vessels, and 3) a small subset of T cells in the peripheral blood. Mouse monoclonal antibodies (two IgGs, one IgM, and F(ab')2 fragments) reacting with GD3 were found to stimulate proliferation of T cells derived from peripheral blood. Proliferation of T cells was observed even in cultures depleted of macrophages, suggesting that activation by anti-GD3 was not dependent on the presence of accessory cells. T cell proliferation was maximum between days 5 and 7 of stimulation and was preceded by expression of interleukin 2 receptors. No stimulation was observed with control antibodies of the identical isotype or with monoclonal antibodies recognizing the gangliosides GD2 or GM2. During stimulation by anti-GD3 monoclonal antibodies, there was an expansion of the GD3+ pool of T cells, but depletion of GD3+ T cells prior to stimulation abrogated the response. Proliferation induced by binding to GD3 could be augmented by exogenous interleukin 2 and phytohemagglutinin. Anti-CD3 (T3) monoclonal antibodies had little or no effect. These results demonstrate that binding to GD3 on the surface of T cells can elicit signals for T cell proliferation.

Antibodies, Monoclonal↗
PubMed1987

Phenotypic heterogeneity of melanoma. Relation to the differentiation program of melanoma cells.

Phenotypic heterogeneity is a characteristic feature of tumor lesions in patients with melanoma. Variability can be observed in cell morphology, pigmentation, and antigen expression. To test whether phenotypic heterogeneity could be the result of events regulated during cell differentiation, we evaluated the expression of a panel of differentiation traits on melanoma cells. Metastatic melanoma lesions from two patients, designated FD and AP, were examined histologically and found to contain mixed populations of cells. Established melanoma cell lines derived from each of these lesions were subcloned at early passage in culture (passages 7 and 8) to create a panel of clones derived from each tumor. There was heterogeneity in the expression of differentiation-related traits in clones, corresponding to distinct phenotypes observed within the original tumors. Clones from patient FD corresponded to early to intermediate stages of melanocyte differentiation, and clones from patient AP ranged from intermediate to late stages. The influence of cholera toxin and PMA on differentiation of parental cultures and subclone was studied. Results of induction studies demonstrated a number of features of differentiation of melanoma cells: regulation of differentiation traits is coordinated as a program of traits expressed sequentially at specific stages; early traits, such as the epidermal growth factor receptor and the melanoma chondroitin sulfate proteoglycan antigen, are downregulated as melanoma cells differentiate, whereas late markers, including melanin, tyrosinase activity, and antigens expressed in mature melanosomes, are upregulated; Ia (class II major histocompatibility) antigens are characteristically expressed on melanomas corresponding to early or intermediate stages of differentiation and are regulated as part of the differentiation program; minimal changes in stage of differentiation were observed during induction of parental cultures with either cholera toxin or PMA, whereas definite shifts in differentiation could be induced in selected cloned subpopulations. We conclude that melanoma cells are not frozen at a specific stage of differentiation, but rather are capable of differentiating when exposed to appropriate signals. Diversity in the differentiation state of melanoma cells can account for much of the phenotypic heterogeneity observed in melanoma lesions.

Antigens, Neoplasm↗
PubMed1987

HIV antigen in the brains of patients with the AIDS dementia complex.

Human immunodeficiency virus infection was identified immunohistochemically in the brains of 8 patients with acquired immune deficiency syndrome dementia complex. Using a monoclonal antibody against a structural viral protein (p25), infection was detected in white matter and basal ganglia in a distribution paralleling that of the major neuropathological abnormalities. Viral antigen was identified principally in perivascular and parenchymal macrophages and in multinucleated cells of macrophage origin that were identified morphologically and by immunocytochemical staining for acid phosphatase isozyme. In 4 of the 8 patients, viral antigen was also detected in acid-phosphatase-negative, process-bearing neuroglial cells; in 2 patients, antigen was detected in basal ganglion cells that were morphologically consistent with neurons and in alkaline-phosphatase-positive cells with elongated nuclei that were most likely of endothelial origin.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Changes in cell surface glycoprotein expression during differentiation of human keratinocytes.

Six cell surface glycoproteins defined by monoclonal antibodies were selected for study on human epidermal cells. In tests on tissue sections, three of the glycoproteins [J143 (gp140/30); T43 (gp85/36); H99 (gp38)] were expressed in the basal cell layer of the epidermis, whereas the other three glycoproteins [T179 (gp140/95); T16 (gp40/50); BT15 (gp80)] were preferentially expressed in maturing keratinocytes above the basal layer. We compared synthesis of these glycoproteins in fresh epidermis and in primary epidermal short term cultures using [35S]methionine for metabolic labeling. Synthesis of J143 was 8- to 20-fold higher and synthesis of T43 was 4- to 10-fold lower in cultured cells compared with fresh epidermis. BT15, an antigen strongly expressed on terminally differentiating keratinocytes, was synthesized at 5- to 15-fold higher levels in fresh epidermis than in cultured cells. Biosynthesis levels of H99, T179, and T16 did not change in cultured epidermal cells. Based on our findings, we propose a model of surface antigenic changes that occur during keratinocyte differentiation in vivo.

Adult↗
PubMed1987

Diagnosis of renal proximal tubular injury by urinary immunoassay for a proximal tubular antigen, the adenosine deaminase binding protein.

A sandwich ELISA assay has been formatted from two commercially available murine monoclonal antibodies, URO-4 and URO-4a, directed against a 120,000 dalton glycoprotein, the adenosine deaminase binding protein (ABP), found on the brush border of the renal proximal tubular epithelial cell. Untimed urine samples from 37 normal individuals and urinary ABP less than 0.1 AU; 37 patients with pure glomerular disease had ABP less than 0.4 AU (with 29, or 76% less than 0.2 AU); 10 patients with pre-renal azotaemia had ABP less than 0.6 (with 8, or 80% less than 0.3 AU). In contrast, 79 patients with post-ischaemic acute tubular necrosis had ABP greater than 0.6 AU. Acute renal failure due to myoglobinuria, contrast dye, and aminoglycoside toxicity were all associated with urinary ABP greater than 1.0 AU. In addition, all six patients with acute bacteraemic pyelonephritis had ABP greater than 0.7 AU, as opposed to ABP less than 0.2 AU in the urines of 12 women with acute cystitis. We conclude that this monoclonal antibody based urinary assay is a sensitive measure of renal proximal tubular injury, reliably distinguishes acute tubular from glomerular disease, and may be helpful in differentiating forms of urinary tract infection.

Acute Kidney Injury↗
PubMed1987

Expression of ras proto-oncogene proteins in normal human tissues.

The expression of ras proto-oncogenes in normal human tissues was studied by immunohistochemical staining and by immunoblotting using monoclonal antibodies. We detected p21ras protein in almost every fetal and adult tissue, but the level varied significantly among cell types. In some cell lineages, immature cells capable of proliferation contain more p21ras than do mature cells. By contrast, certain fully differentiated cells, such as neurons and the epithelial cells of endocrine glands, express abundant p21ras. Among mammalian tissues the highest level of ras protein was detected in brain. Crude synaptosomal membrane preparations from rat brain contain substantially more p21ras than do plasma membranes from rat liver. The observed distribution of p21ras suggests a role for these proteins both in cellular proliferation and in certain specialized cellular functions.

Antibodies, Monoclonal↗